Liver Failure

Question 1

What is liver failure?

Answer 1

• Severe liver dysfunction leading to jaundice, encephalopathy (damage or disease that affects the brain) and coagulopathy (condition that affects how your blood clots, resulting in more bleeding)
• Can occur suddenly in a previously healthy liver (acute liver failure) but more often occurs as a result of decompensation of chronic liver disease (acute-on-chronic hepatic failure)

Question 2

How is liver failure classified?

Answer 2

1. Acute: if onset of symptoms is in <26 weeks(6 months) in a patient with a previously healthy liver
   - Hyperacute (<7 days)
   - Acute (1-4 weeks)
   - Subacute (4-12 weeks)
2. Chronic liver failure is the onset of liver failure on a background of cirrhosis

Question 3

What is chronic liver disease?

Answer 3

Chronic Liver Disease ⇒ condition characterized by progressive deterioration of hepatic function over at least 26–28 weeks (∼ 6 months). eg. cirrhosis.
- Stigmata of Chronic Liver Disease = spider naevi, gynaecomastia, dupuytren’s contracture, palmar erythema
- Signs of Decompensation = ascites, jaundice, encephalopathy

Question 4

What are some of the causes of liver failure?

Answer 4

Viral hepatitis (usually A/B), paracetamol overdose/overuse (50% of ALF in UK), idiopathic, alcohol excess, acute fatty liver of pregnancy

• Infection (Hepatitis A, B and E, CMV, yellow fever, leptospirosis)
  -Drugs (Paracetamol overdose, halothane,isoniazid, MDMA, alcohol)
• Toxins (Amanita phalloides mushroom, carbon tetrachloride)
• Vascular (Budd-Chiari syndrome)
• Primary biliary cirrhosis
• Haemochromatosis
• Wilson’s disease
• Autoimmune hepatitis
• Alpha-1 antitrypsin deficiency
• Non-alcoholic fatty liver disease
• Fatty liver of pregnancy
• Malignancy
• HELLP syndrome (HELLP syndrome is a complication of pregnancy characterised by Haemolysis, Elevated Liver Enzymes and Low Platelets and is mostly seen in the third trimester)

Question 5

What are causes of liver failure?

Answer 5

1. Viral
   - Hepatitis A, B, C, D and E
2. Drugs
   - Paracetamol overdose
   - Idiosyncratic drug reactions e.g. anti-TB therapy
3. Less common causes
   - Autoimmune hepatitis
   - Budd-Chiari syndrome
   - Pregnancy-related
   - Malignancy (e.g. lymphoma)
   - Haemochromatosis
   - Mushroom poisoning (Amanita phalloides)
   - Wilson’s disease

Question 6

What is the pathogenesis of the manifestations of liver failure?

Answer 6

1. Jaundice - due to decreased secretion of conjugated bilirubin (decreased ability og liver to conjugate bilirubin= the presence of conjugated and unconjugated bilirubin in the blood)
2. Encephalopathy
   - Nitrogenous products (e.g. ammonia) is absorbed in the gut and goes via the portal circulation to the liver
   - A normal liver would be able extract these harmful substances
   - However, if the liver is failing, these toxic products can go through the liver and reach the brain and exert its effects
3. Coagulopathy
   - Reduced synthesis of clotting factors
   - Reduced platelets
   - Platelet functional abnormalities associated with jaundice or renal failure

Question 7

Summarise the epidemiology of liver failure

Answer 7

Paracetamol overdose counts for 50% of acute liver failure in the UK

Question 8

What are the presenting symptoms of liver failure

Answer 8

• May be asymptomatic
• Fever
• Nausea
• Jaundice (not always)

Question 9

What signs of liver failure can be found on physical examination

Answer 9

• Jaundice
• Encephalopathy
• Asterixis
• Fetor hepaticus (smell of pear drops)
• Ascites and splenomegaly (less common if acute or hyperacute)
• Bruising or bleeding
• Signs of secondary causes (e.g. bronze skin colour, Kayser-Fleisher rings)
• Pyrexia - may indicate infection or liver necrosis

Question 10

What investigations are used to diagnose/ monitor liver failure?

Answer 10

1. Prothrombin Time → raised indicated coagulopathy. Best indicator of liver function.
2. LFTs → high bilirubin, AST, ALT, ALP, GGT. Low albumin (Leads to Leukonychia).
3. Hypoglycaemia
4. Identify Cause → viral serology, paracetamol levels
5. EEG → monitor encephalopathy

Question 11

How is liver failure managed?

Answer 11

1. N-acetylcysteine → treatment for paracetamol overdose
2. Encephalopathy → give lactulose. IV Mannitol can help reduce cerebral oedema.
3. Coagulopathy → vitamin K and Fresh frozen plasma
4. Liver Transplant → considered in most patients

Question 12

What are some of the possible complications of liver failure

Answer 12

• Infection
• Coagulopathy
• Hypoglycaemia
• Disturbance of electrolyte balance and acid-base balance
• Disturbance of cardiovascular system
• Hepatorenal syndrome
• Cerebral oedema (causing raised ICP) – as liver fails, nitrogenous waste builds up and passes to the brain where astrocytes clear it by processes involving conversion of glutamate to glutamine. This excess glutamine causes an osmotic imbalance and a shift of fluid into the cells – cerebral oedema
• Respiratory failure
• Decompensated liver disease is a major risk factor for spontaneous bacterial peritonitis, which is confirmed with a tap and neutrophil count >250 cells/mm3

Question 13

Summarise the prognosis for patients with liver failure

Answer 13

Depends on severity and aetiology

Question 14

What is the criteria to qualify for a liver transplant?

Answer 14

The King’s College Hospital Criteria for Liver Transplant (paracetamol induced):

Arterial pH <7.3 at 24h after ingestion
OR

Pro-thrombin time >100s AND
Creatinine >300µmol/L AND
Grade III or IV encephalopathy